For many breast cancer patients, a single positive molecular test — a protein sample known as ImmunoHistoChemistry (IHC) — is enough to determine that Herceptin should be used as therapy, say researchers from Mayo Clinic. However, if the test is negative, then a second test to check for HER2 genes should be ordered, they say.
Currently, many physicians use as many as three different tests together, which adds considerable expense to breast cancer treatment, say the researchers, who published their findings online August 9 in the Journal of Clinical Oncology (JCO).
The researchers specifically found that both IHC and a Fluorescence In Situ Hybridization (FISH) test equally predicted if a patient would benefit from Herceptin, and that a third test to measure chromosome 17 copy number is not helpful at all.
But given that an IHC test costs much less than a FISH analysis, it makes economic sense for oncologists to use an IHC test first, says the study’s lead investigator, Edith Perez, M.D., a breast cancer researcher at the Mayo Clinic campus in Florida. Robert Jenkins, M.D., Ph.D., a professor of laboratory genetics at Mayo Clinic in Rochester, Minn., is a co-lead investigator as part of Perez’ team.
“If the IHC test scores 3 (which is regarded as a positive protein test) there is no reason to offer the much more expensive FISH test,” Dr. Perez says. “Now, typically, many physicians want to “verify” positive IHC findings with FISH, or use FISH first, which some inaccurately regard as a more accurate test, and this study shows that is unnecessary and costly.
“Our data are very important for clinical practice,” she says. “They likely will change how these tests are ordered, which will result in savings for individual patients as well as for the nation.”
There has been longstanding confusion over testing for HER2, the researchers say. IHC measures how much HER2 protein there is on the surface of cancer cells, and FISH checks to see if cancer cells have extra copies of the HER2 gene. The chromosome 17 analyses also looks for extra copies of that chromosome because it contains the HER2 gene.
There has been longstanding confusion over testing for HER2, the researchers say. IHC measures how much HER2 protein there is on the surface of cancer cells, and FISH checks to see if cancer cells have extra copes of the HER2 gene. The chromosome 17 analyses also looks for extra copies of that chromosome because it contains the HER2 gene.
The study is a follow-up analysis of N9831, a federally funded clinical trial in which 1,888 patients with stage I-III invasive HER2+ breast cancer were randomized to be treated with either chemotherapy alone or chemotherapy with sequential or concurrent use of Herceptin. The agent is designed to treat the 20 percent of breast cancer that is fueled by HER2 growth factor proteins.
Researchers from Mayo Clinic, along with their nationwide collaborators, compared disease-free survival from Herceptin in patients randomized to use it with scores from their IHC and FISH tests, which were analyzed by a central laboratory at Mayo Clinic.
Not only did they find that IHC and FISH equally predicted Herceptin benefit, they also discovered that, in FISH, degree of benefit was not associated with the number of HER2 gene copies in a cancer cell. “People had thought that having more copies of the gene would predict for better efficacy of adjuvant Herceptin,” Dr. Perez says. “We proved that idea to be wrong and that is a potential clinical practice-altering observation. Patients with low levels of HER2 gene copies were just as likely to be free of disease relapse after receiving Herceptin added to chemotherapy as were patients with high levels of HER2 gene amplification.”
She adds that the study findings suggest that IHC should be used first, not only because of expense but because as many as 5 to 8 percent of patients with a normal FISH finding have HER2 protein over-expression, which the IHC test would pick up.
Additionally, Perez says the study’s findings suggest that if initial IHC scores are lower than 3, then it makes sense to follow-up with a FISH analysis to help understand Herceptin benefit.
The study was funded by The National Institutes of Health, the Breast Cancer Research Foundation, the National Cancer Institute and Genentech.
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